Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derive...Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derived vesicles(MDVs)are an emerging subpopulation of extracellular vesicle(EV)first discovered in 2008 that allow mitochondria to communicate with their surroundings.展开更多
1.Background The United Nations(UN)2030 Agenda for Sustainable Development,adopted in 2015,established the Sustainable Development Goals(SDGs)as a comprehensive framework to address global challenges through interconn...1.Background The United Nations(UN)2030 Agenda for Sustainable Development,adopted in 2015,established the Sustainable Development Goals(SDGs)as a comprehensive framework to address global challenges through interconnected social,economic,and environmental targets.展开更多
BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite imp...BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.展开更多
Optogenetics has revolutionized the field of neuroscience by enabling precise control of neural activity through light-sensitive proteins known as opsins.This review article discusses the fundamental principles of opt...Optogenetics has revolutionized the field of neuroscience by enabling precise control of neural activity through light-sensitive proteins known as opsins.This review article discusses the fundamental principles of optogenetics,including the activation of both excitatory and inhibitory opsins,as well as the development of optogenetic models that utilize recombinant viral vectors.A considerable portion of the article addresses the limitations of optogenetic tools and explores strategies to overcome these challenges.These strategies include the use of adeno-associated viruses,cell-specific promoters,modified opsins,and methodologies such as bioluminescent optogenetics.The application of viral recombinant vectors,particularly adeno-associated viruses,is emerging as a promising avenue for clinical use in delivering opsins to target cells.This trend indicates the potential for creating tools that offer greater flexibility and accuracy in opsin delivery.The adaptations of these viral vectors provide advantages in optogenetic studies by allowing for the restricted expression of opsins through cell-specific promoters and various viral serotypes.The article also examines different cellular targets for optogenetics,including neurons,astrocytes,microglia,and Schwann cells.Utilizing specific promoters for opsin expression in these cells is essential for achieving precise and efficient stimulation.Research has demonstrated that optogenetic stimulation of both neurons and glial cells-particularly the distinct phenotypes of microglia,astrocytes,and Schwann cells-can have therapeutic effects in neurological diseases.Glial cells are increasingly recognized as important targets for the treatment of these disorders.Furthermore,the article emphasizes the emerging field of bioluminescent optogenetics,which combines optogenetic principles with bioluminescent proteins to visualize and manipulate neural activity in real time.By integrating molecular genetics techniques with bioluminescence,researchers have developed methods to monitor neuronal activity efficiently and less invasively,enhancing our understanding of central nervous system function and the mechanisms of plasticity in neurological disorders beyond traditional neurobiological methods.Evidence has shown that optogenetic modulation can enhance motor axon regeneration,achieve complete sensory reinnervation,and accelerate the recovery of neuromuscular function.This approach also induces complex patterns of coordinated motor neuron activity and promotes neural reorganization.Optogenetic approaches hold immense potential for therapeutic interventions in the central nervous system.They enable precise control of neural circuits and may offer new treatments for neurological disorders,particularly spinal cord injuries,peripheral nerve injuries,and other neurodegenerative diseases.展开更多
Mount Kandil is situated in the eastern sector of the EAHP(Eastern Anatolian High Plateau),to the south of the Lesser Caucasus.The mountain lies at the westernmost end of the Aras Mountains,which extends approximately...Mount Kandil is situated in the eastern sector of the EAHP(Eastern Anatolian High Plateau),to the south of the Lesser Caucasus.The mountain lies at the westernmost end of the Aras Mountains,which extends approximately 80 km along a NW-SE axis.With a summit reaching~3214 m(a.s.l.),Mount Kandil is a stratovolcano that,like many other peaks within the EAHP and the Lesser Caucasus,experienced significant environmental changes during Late Pleistocene.Among these,glacial processes stand out as the most profound,having distinctly shaped the mountains geomorphic landscape.This study presents,for the first time,a comprehensive analysis of the glacial morphology of Mount Kandil based on multiple datasets.Field-based morphological observations indicate that an area of approximately 32.62 km^(2)has been sculpted by glacial activity.Within six glaciated regions on Mount Kandil,25 cirques and 6 glacial valleys have been identified.In addition,moraines in various locations exhibit characteristic morphologies.Furthermore,valley glaciers are inferred to have descended to altitudes as low as~2000 m.The paleoequilibrium line(p ELA)was estimated to use AABR method within GIS,yielding a mean pELA of~2730 m.Ice thickness modelling indicates that the thickness of glaciers in the Kandil Mountain valleys reaches up to~350 m.Due to its orographic extension,Mount Kandil is exposed to humid northwest winds and receives substantial frontal precipitation(~686 mm annually).The compiled geomorphic,cartographic and morphometric parameters suggest that the glaciation dynamics of Mount Kandil—situated between the Southeastern Taurus and the Lesser Caucasus—closely resemble those observed in the Lesser Caucasus.This indicates that glaciation was primarily governed by northern atmospheric systems with additional influences from southerly or westerly winds.The integrated data also underscores the role of multiple atmospheric systems in controlling the glaciation regime around the Lesser Caucasus.Additionally,findings on regional pELA question the common belief that pELA increases eastward in EAHP.展开更多
Tuberculosis(TB),one of the oldest infectious diseases caused by Mycobacterium tuberculosis,poses a considerable challenge to global public health.There are approximately 10 million new TB cases worldwide annually,and...Tuberculosis(TB),one of the oldest infectious diseases caused by Mycobacterium tuberculosis,poses a considerable challenge to global public health.There are approximately 10 million new TB cases worldwide annually,and TB claims the lives of nearly 3 million people each year,making it one of the leading causes of death from a single infectious disease[1].China ranks third globally in terms of TB burden,with approximately 733,000 TB cases reported in 2023[2].Based on the ecological model of health determinants developed by Whitehead and Dahlgren,health determinants can be classified into direct causes.展开更多
The Smiles rearrangement is an exceptionally versatile method in organic synthesis,providing a broad canvas for designing cascade reactions that construct new Csp^(2)-Y(Y=C,O,N,S,CO,etc.)bonds.Among the various types ...The Smiles rearrangement is an exceptionally versatile method in organic synthesis,providing a broad canvas for designing cascade reactions that construct new Csp^(2)-Y(Y=C,O,N,S,CO,etc.)bonds.Among the various types of Smiles rearrangement,the radical-type variant has emerged as a more powerful,mild,efficient,and modern synthetic technique compared to its traditional ionic counterpart.This approach excels in generating new(hetero)aromatic migration products,enabling significant advancements in recent years.This tutorial review focuses on the recent progress,since 2016,in the development and application of radical Smiles rearrangement in organic chemistry.Special attention is paid to novel transformations achieved through photochemical,electrochemical,and transition metal catalysis methods.展开更多
Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological prop...Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological properties and tissue specificity,highlighting its potential as a biomedical material for the repair of severe peripheral nerve injury;however,its role in modulating neuroinflammation post-peripheral nerve injury remains unknown.Here,we aimed to characterize the anti-inflammatory properties of porcine decellularized nerve matrix hydrogel and their underlying molecular mechanisms.Using peripheral nerve injury model rats treated with porcine decellularized nerve matrix hydrogel,we evaluated structural and functional recovery,macrophage phenotype alteration,specific cytokine expression,and changes in related signaling molecules in vivo.Similar parameters were evaluated in vitro using monocyte/macrophage cell lines stimulated with lipopolysaccharide and cultured on porcine decellularized nerve matrix hydrogel-coated plates in complete medium.These comprehensive analyses revealed that porcine decellularized nerve matrix hydrogel attenuated the activation of excessive inflammation at the early stage of peripheral nerve injury and increased the proportion of the M2 subtype in monocytes/macrophages.Additionally,porcine decellularized nerve matrix hydrogel negatively regulated the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB axis both in vivo and in vitro.Our findings suggest that the efficacious anti-inflammatory properties of porcine decellularized nerve matrix hydrogel induce M2 macrophage polarization via suppression of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway,providing new insights into the therapeutic mechanism of porcine decellularized nerve matrix hydrogel in peripheral nerve injury.展开更多
Forests are experiencing more frequent and intense wildfires in Canada,which pose considerable threats to water quantity and quality,particularly during the summer low-flow period when water demand is high.While the i...Forests are experiencing more frequent and intense wildfires in Canada,which pose considerable threats to water quantity and quality,particularly during the summer low-flow period when water demand is high.While the impacts of wildfire on hydrology have been widely assessed at the watershed scale,the underlying mechanisms of the responses of summer low flows remain poorly understood.In this study,we employed an integrated research framework that combines hydrometric monitoring with geochemical tracing to evaluate how the 2021 White Rock Lake Wildfire affected summer low flows,and to identify the underlying mechanisms governing these responses in the Okanagan Valley,British Columbia(BC),Canada.We found that(1)summer low flows,represented by Q90(flows exceeded at 90%of the time in summer)significantly increased following the wildfire(p<0.05);(2)summer low flows were primarily regulated by snow water in early summer(July),while dominated by groundwater in late summer(August and September);and(3)enhanced snow water contribution and reduced evapotranspiration(ET)were two primary contributors to the increased summer low flows.Our results provide insights for developing sustainable water management strategies for the region in the context of climate change and increasing forest disturbance.This study also demonstrates that the combination of hydrometric monitoring and geochemical tracing is an effective approach towards uncovering mechanisms that drive low-flow responses.展开更多
The poor electrical conductivity of metal-organic frameworks(MOFs)limits their electrocatalytic performance in the oxygen evolution reaction(OER).In this study,a Py@Co-MOF composite material based on pyrene(Py)molecul...The poor electrical conductivity of metal-organic frameworks(MOFs)limits their electrocatalytic performance in the oxygen evolution reaction(OER).In this study,a Py@Co-MOF composite material based on pyrene(Py)molecules and{[Co2(BINDI)(DMA)_(2)]·DMA}_(n)(Co-MOF,H4BINDI=N,N'-bis(5-isophthalic acid)naphthalenediimide,DMA=N,N-dimethylacetamide)was synthesized via a one-pot method,leveragingπ-πinteractions between pyrene and Co-MOF to modulate electrical conductivity.Results demonstrate that the Py@Co-MOF catalyst exhibited significantly enhanced OER performance compared to pure Co-MOF or pyrene-based electrodes,achieving an overpotential of 246 mV at a current density of 10 mA·cm^(-2) along with excellent stability.Density functional theory(DFT)calculations reveal that the formation of O*in the second step is the rate-determining step(RDS)during the OER process on Co-MOF,with an energy barrier of 0.85 eV due to the weak adsorption affinity of the OH*intermediate for Co sites.CCDC:2419276.展开更多
BACKGROUND Peripheral endovascular intervention(PEVI)is performed using radiation.Radiation has deleterious health consequences for patients and operators.AIM To investigate the gender radiation disparities and proced...BACKGROUND Peripheral endovascular intervention(PEVI)is performed using radiation.Radiation has deleterious health consequences for patients and operators.AIM To investigate the gender radiation disparities and procedural outcomes in PEVI.METHODS A prospective observational study was performed in 186 consecutive patients(65±12 years)at an academic medical center from January 2019 to April 2020(mean follow-up of 3.9±3.6 months)comparing the gender radiation disparity and outcomes of PEVI(n=147 underwent intervention,79.0%).Groups were divided into women(n=99,53.2%)and men(n=87,48.4%).Primary endpoints included air kerma,dose area product(DAP),fluoroscopy time,and contrast use.Secondary endpoints included all-cause mortality,acute myocardial infarction,acute kidney injury,stroke,repeat revascularization,major adverse limb event,and the composite of complications.RESULTS Men showed increased DAP compared with women(15221.2±25858.5µGy×m^(2) vs 9251.7±9555.3µGy×m^(2),P=0.047),but no significant difference in air kerma or any other primary endpoints.In the secondary endpoints,no significant diffe-rence was found between gender.CONCLUSION Men had increased DAP indicating more radiation absorption in the exposed area.Gender outcomes showed no difference in complications.Thus,PEVI can be safely performed in men or women.展开更多
Xylogenesis,the process through which wood cells are formed,results in the long-term storage of carbon in woody biomass,making it a key component of the global carbon cycle.Understanding how environmental drivers infl...Xylogenesis,the process through which wood cells are formed,results in the long-term storage of carbon in woody biomass,making it a key component of the global carbon cycle.Understanding how environmental drivers influence xylogenesis during the growing season is therefore of great interest.However,studying shortterm drivers of wood production using xylogenetic data is complicated by the usual sampling scheme and the influence of eccentric growth,i.e.,heterogeneous growth around the stem.In this study,we improve xylogenesis research by introducing a statistical approach that explicitly considers seasonal phenology,short-term growth rates,and growth eccentricity.To this end,we developed Bayesian models of xylogenesis and compared them with a conventional method based on the use of Gompertz functions.Our results show that eccentricity generated high temporal autocorrelation between successive samples,and that explicitly taking it into account improved both the representativeness of phenology and intra-ring variability.We observed consistent short-term patterns in the model residuals,suggesting the influence of an unaccounted-for environmental variable on cell production.The proposed models offer several advantages over traditional methods,including robust confidence intervals around predictions,consistency with phenology,and reduced sensitivity to extreme observations at the end of the growing season,often linked to eccentric growth.These models also provide a benchmark for mechanistic testing of short-term drivers of wood formation.展开更多
Large-scale CO_(2)emissions have exacerbated the greenhouse effect,reinforcing the critical need for efficient CO_(2)mitigation methods.Plasma-catalytic technology enables CO_(2)conversion under mild conditions,especi...Large-scale CO_(2)emissions have exacerbated the greenhouse effect,reinforcing the critical need for efficient CO_(2)mitigation methods.Plasma-catalytic technology enables CO_(2)conversion under mild conditions,especially for CO_(2)methanation(the Sabatier reaction),which has attracted significant attention due to its economic benefits and the potential for safe energy transportation via existing natural gas pipelines.The development of high-performance CO_(2)methanation catalysts remains an ongoing and long-term objective,and there is a lack of adequate in-situ characterization techniques to investigate the mechanisms.This study focuses on the Ni/La_(2)O_(3)(LN)catalyst and introduces two CO_(2)activation strategies through F and Na modifications:the Ni-Ov-Ni site activation with electron transfer from Ni0 under low-power conditions and basic site activation under high-power conditions.The LN-NaF catalysts enhance CO_(2)methanation activity across the entire power range compared to LN,achieving a CO_(2)conversion of 86.3%and CH4 selectivity of 99.4%.Additionally,LN-F(h)reaches a CH4 yield 4.15 times higher than that of LN at low power.Furthermore,in-situ diffuse reflectance infrared Fourier transform(DRIFT)spectroscopy with a self-made reactor are performed under plasma-catalytic conditions to reveal the CO_(2)adsorption and conversion mechanisms,indicating that different dopants(F,Na,and NaF)exhibit promoting effects on different intermediates,resulting in variations in CO_(2)methanation activity.This study provides valuable insights for improving catalyst performance and a thorough comprehension of mechanisms in CO_(2)methanation.展开更多
AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analy...AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analysis.METHODS:The causal effects of several behavioral factors,including screen time,education time,time spent outdoors,and physical activity,on the risk of HM using univariable Mendelian randomization(MR)and MVMR analyses were first assessed.Genome-wide association study summary statistics of serum metabolites were also used in mediation analysis to determine the extent to which serum metabolites mediate the effects of behavioral factors on HM.RESULTS:MR analyses indicated that both increased time spent outdoors and a higher frequency of moderate physical activity significantly reduced the risk of HM.Further MVMR analysis confirmed that moderate physical activity independently contributed to a lower risk of HM.Additionally,MR analyses identified 13 serum metabolites significantly associated with HM,of which 12 were lipids and one was an amino acid derivative.Mediation analysis revealed that six lipid metabolites mediated the protective effects of moderate physical activity on HM,with the highest mediation proportion observed for 1-(1-enyl-palmitoyl)-GPC(p-16:0;30.83%).CONCLUSION:This study suggests that in addition to outdoor time,moderate physical activity habits may have an independent protective effect against HM and pointed to lipid metabolites as priority targets for the prevention due to low physical activity.These results emphasize the importance of physical activity and metabolic health in HM and underscore the need for further study of these complex associations.展开更多
Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response pla...Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response plays a crucial role in worsening brain injury.Neuroinflammation,a key player in the pathophysiology of stroke,has a dual role.In the acute phase of stroke,neuroinflammation exacerbates brain injury,contributing to neuronal damage and blood–brain barrier disruption.This aspect of neuroinflammation is associated with poor neurological outcomes.Conversely,in the recovery phase following stroke,neuroinflammation facilitates brain repair processes,including neurogenesis,angiogenesis,and synaptic plasticity.The transition of neuroinflammation from a harmful to a reparative role is not well understood.Therefore,this review seeks to explore the mechanisms underlying this transition,with the goal of informing the development of therapeutic interventions that are both time-and context-specific.This review aims to elucidate the complex and dual role of neuroinflammation in stroke,highlighting the main actors,biomarkers of the disease,and potential therapeutic approaches.展开更多
Artificial intelligence(AI)-augmented contrast-enhanced ultrasonography(CEUS)is emerging as a powerful tool in liver imaging,particularly in enhancing the accuracy of Liver Imaging Reporting and Data System(known as L...Artificial intelligence(AI)-augmented contrast-enhanced ultrasonography(CEUS)is emerging as a powerful tool in liver imaging,particularly in enhancing the accuracy of Liver Imaging Reporting and Data System(known as LI-RADS)classi-fication.This review synthesized published data on the integration of machine learning and deep learning techniques into CEUS,revealing that AI algorithms can improve the detection and quantification of contrast enhancement patterns.Such improvements led to more consistent LI-RADS categorization,reduced interoperator variability,and enabled real-time analysis that streamlined work-flow.The enhanced sensitivity of AI tools facilitated better differentiation between benign and malignant lesions,ultimately optimizing patient management.These advances suggest that AI-augmented CEUS could transform liver imaging by providing rapid,reliable,and objective assessments.However,the review also highlighted the need for further large-scale,multicenter studies to fully validate these findings and ensure the safe integration of AI into routine clinical practice.INTRODUCTION International hepatology society guidelines have established contrast-enhanced computed tomography(CT)and contrast-enhanced magnetic resonance imaging(MRI)as the imaging modalities of choice for diagnosing hepatocellular carcinoma(HCC)lesions larger than 1 cm.MRI remains the gold standard for detecting small HCC nodules in cirrhotic livers due to its superior soft-tissue contrast and functional imaging capabilities.However,early or atypical presentations remain challenging for differential diagnosis,staging,and treatment planning.In these scenarios contrast-enhanced ultrasonography(CEUS)is a valuable second-line tool,offering real-time,radiation-free evaluation and repeatability for follow-up.A recent meta-analysis of head-to-head studies reported comparable diagnostic performance between CEUS and CT/MRI with pooled sensitivities and specificities of 0.67/0.88 for CEUS vs 0.60/0.98 for CT/MRI in non-HCC malignancies,and similar specificities for HCC diagnosis(0.70 for CEUS vs 0.59 for CT;0.81 for CEUS vs 0.79 for MRI)[1].Given the limitations of individual imaging modalities,hybrid techniques and multimodal approaches are gaining traction for improving lesion detection,especially in cases where standard methods fall short.Artificial intelligence(AI)has emerged as a powerful tool in medical imaging,enhancing diagnostic accuracy and reliability across platforms.In CEUS liver imaging dynamic enhancement patterns often challenge consistent interpretation across observers.AI holds particular promise for standardizing assessments.The growing complexity of liver tumor evaluation has also driven interest in approaches that integrate serum bio-markers with advanced imaging.However,no single strategy currently meets all the diagnostic and prognostic re-quirements.Recent studies highlighted the potential of AI to bridge this gap by enabling precise image interpretation and facilitating the integration of heterogeneous clinical and imaging data[2].Altogether the convergence of CEUS with AI and radiomics offers a dynamic,quantitative,and potentially reproducible paradigm for liver lesion assessment,comple-menting traditional imaging methods.This review aimed to provide an overview of current advances in AI-driven CEUS for liver lesion assessment with a particular focus on automated Liver Imaging Reporting and Data System(LI-RADS)classification,radiomics-based models,and future clinical integration.While another recent systematic review[3]provided a comprehensive analysis of AI applications in CEUS,our approach offers a targeted perspective,emphasizing LI-RADS-centered scoring,automated lesion characterization,and clinical utility,particularly in the context of HCC diagnosis and management.In the methodological process of this narrative mini-review,the literature selection was primarily based on targeted PubMed searches.ChatGPT-4o(OpenAI)[4]was employed to assist in refining query parameters and identifying relevant,up-to-date peer-reviewed sources on CEUS-based AI applications.展开更多
Cirrhosis represents the end stage of chronic liver disease,significantly reducing life expectancy as it progresses from a compensated to a decompensated state,leading to serious complications.Recent improvements in m...Cirrhosis represents the end stage of chronic liver disease,significantly reducing life expectancy as it progresses from a compensated to a decompensated state,leading to serious complications.Recent improvements in medical treatment have created a shift in cirrhosis management.Various causes,including hepatitis viruses,alcohol consumption,and fatty liver disease,contribute to cirrhosis and are closely linked to liver cancer.The disease develops through hepatocyte necrosis and regeneration,resulting in fibrosis and sinusoidal capillarization,leading to portal hypertension and complications such as ascites,hepatic encephalopathy,and organ dysfunction.Cirrhosis also holds an increased risk of hepatocellular carcinoma.Diagnosing cirrhosis involves assessing fibrosis scores through blood tests and measuring liver stiffness through elastography.Liver transplantation is the definitive treatment for endstage liver disease and acute liver failure.展开更多
A novel siphon-based divide-and-conquer(SbDaC)policy is presented in this paper for the synthesis of Petri net(PN)based liveness-enforcing supervisors(LES)for flexible manufacturing systems(FMS)prone to deadlocks or l...A novel siphon-based divide-and-conquer(SbDaC)policy is presented in this paper for the synthesis of Petri net(PN)based liveness-enforcing supervisors(LES)for flexible manufacturing systems(FMS)prone to deadlocks or livelocks.The proposed method takes an uncontrolled and bounded PN model(UPNM)of the FMS.Firstly,the reduced PNM(RPNM)is obtained from the UPNM by using PN reduction rules to reduce the computation burden.Then,the set of strict minimal siphons(SMSs)of the RPNM is computed.Next,the complementary set of SMSs is computed from the set of SMSs.By the union of these two sets,the superset of SMSs is computed.Finally,the set of subnets of the RPNM is obtained by applying the PN reduction rules to the superset of SMSs.All these subnets suffer from deadlocks.These subnets are then ordered from the smallest one to the largest one based on a criterion.To enforce liveness on these subnets,a set of control places(CPs)is computed starting from the smallest subnet to the largest one.Once all subnets are live,this process provides the LES,consisting of a set of CPs to be used for the UPNM.The live controlled PN model(CPNM)is constructed by merging the LES with the UPNM.The SbDaC policy is applicable to all classes of PNs related to FMS prone to deadlocks or livelocks.Several FMS examples are considered from the literature to highlight the applicability of the SbDaC policy.In particular,three examples are utilized to emphasize the importance,applicability and effectiveness of the SbDaC policy to realistic FMS with very large state spaces.展开更多
Automated and accurate movie genre classification is crucial for content organization,recommendation systems,and audience targeting in the film industry.Although most existing approaches focus on audiovisual features ...Automated and accurate movie genre classification is crucial for content organization,recommendation systems,and audience targeting in the film industry.Although most existing approaches focus on audiovisual features such as trailers and posters,the text-based classification remains underexplored despite its accessibility and semantic richness.This paper introduces the Genre Attention Model(GAM),a deep learning architecture that integrates transformer models with a hierarchical attention mechanism to extract and leverage contextual information from movie plots formulti-label genre classification.In order to assess its effectiveness,we assessmultiple transformer-based models,including Bidirectional Encoder Representations fromTransformers(BERT),ALite BERT(ALBERT),Distilled BERT(DistilBERT),Robustly Optimized BERT Pretraining Approach(RoBERTa),Efficiently Learning an Encoder that Classifies Token Replacements Accurately(ELECTRA),eXtreme Learning Network(XLNet)and Decodingenhanced BERT with Disentangled Attention(DeBERTa).Experimental results demonstrate the superior performance of DeBERTa-based GAM,which employs a two-tier hierarchical attention mechanism:word-level attention highlights key terms,while sentence-level attention captures critical narrative segments,ensuring a refined and interpretable representation of movie plots.Evaluated on three benchmark datasets Trailers12K,Large Movie Trailer Dataset-9(LMTD-9),and MovieLens37K.GAM achieves micro-average precision scores of 83.63%,83.32%,and 83.34%,respectively,surpassing state-of-the-artmodels.Additionally,GAMis computationally efficient,requiring just 6.10Giga Floating Point Operations Per Second(GFLOPS),making it a scalable and cost-effective solution.These results highlight the growing potential of text-based deep learning models in genre classification and GAM’s effectiveness in improving predictive accuracy while maintaining computational efficiency.With its robust performance,GAM offers a versatile and scalable framework for content recommendation,film indexing,and media analytics,providing an interpretable alternative to traditional audiovisual-based classification techniques.展开更多
Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment...Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.展开更多
基金supported by project Emerging Infectious Diseases One Health Basic and Translational Research Actions addressing Unmet Needs on Emerging Infectious Diseases,INF-ACT,Spoke 1 and Spoke 5,Project number PE00000007,CUP B53C20040570005(to PP and DN).
文摘Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derived vesicles(MDVs)are an emerging subpopulation of extracellular vesicle(EV)first discovered in 2008 that allow mitochondria to communicate with their surroundings.
文摘1.Background The United Nations(UN)2030 Agenda for Sustainable Development,adopted in 2015,established the Sustainable Development Goals(SDGs)as a comprehensive framework to address global challenges through interconnected social,economic,and environmental targets.
文摘BACKGROUND Post-transplant tertiary hyperparathyroidism(PT-tHPT)is a well-recognized complication following kidney transplantation,characterized by persistent excessive secretion of parathyroid hormone(PTH)despite improved renal function.It is potentially associated with an increased risk of cardiovascular events,renal osteodystrophy,pathologic fractures,graft loss,and mortality.AIM To evaluate the incidence,risk factors,and outcomes of PT-tHPT amongst kidney transplant recipients.METHODS A total of 887 transplant recipients who underwent transplantation between 2000 and 2020 were evaluated.Univariable and multivariable logistic regression was performed to determine the predictors of tertiary hyperparathyroidism.Graft and recipient outcomes were assessed using multivariable Cox regression.A separate multivariable Cox regression was performed to determine the effect of treatment strategies on outcomes.RESULTS PT-tHPT,defined as elevated PTH(>65 ng/L)and persistent hypercalcemia(>2.60 mmol/L),was diagnosed in 14%of recipients.Risk factors for PT-tHPT included older age[odds ratio(OR)=1.36,P<0.001],Asian ethnicity(OR=0.33,P=0.006),total ischemia time(OR=1.03,P=0.048 per hour),pre-transplant serum calcium(OR=1.38,P<0.001)per decile increase,pre-transplant PTH level(OR=1.31,P<0.001)per decile increase,longer dialysis duration(OR=1.12,P=0.002)per year,history of acute rejection(OR=2.37,P=0.012),and slope of estimated glomerular filtration rate change(OR=0.91,P=0.001).There were a 3.4-fold higher risk of death-censored graft loss and a 1.9-fold greater risk of recipient death with PT-tHPT.The three treatment strategies of conservative management,calcimimetic and parathyroidectomy did not significantly change the graft or patient outcome.CONCLUSION Pretransplant elevated calcium and PTH levels,older age and dialysis duration are associated with PT-tHPT.While PT-tHPT significantly affects graft and recipient survival,the treatment strategies did not affect survival.
基金supported by a grant from the Russian Science Foundation,No.23-75-10041(to MY)。
文摘Optogenetics has revolutionized the field of neuroscience by enabling precise control of neural activity through light-sensitive proteins known as opsins.This review article discusses the fundamental principles of optogenetics,including the activation of both excitatory and inhibitory opsins,as well as the development of optogenetic models that utilize recombinant viral vectors.A considerable portion of the article addresses the limitations of optogenetic tools and explores strategies to overcome these challenges.These strategies include the use of adeno-associated viruses,cell-specific promoters,modified opsins,and methodologies such as bioluminescent optogenetics.The application of viral recombinant vectors,particularly adeno-associated viruses,is emerging as a promising avenue for clinical use in delivering opsins to target cells.This trend indicates the potential for creating tools that offer greater flexibility and accuracy in opsin delivery.The adaptations of these viral vectors provide advantages in optogenetic studies by allowing for the restricted expression of opsins through cell-specific promoters and various viral serotypes.The article also examines different cellular targets for optogenetics,including neurons,astrocytes,microglia,and Schwann cells.Utilizing specific promoters for opsin expression in these cells is essential for achieving precise and efficient stimulation.Research has demonstrated that optogenetic stimulation of both neurons and glial cells-particularly the distinct phenotypes of microglia,astrocytes,and Schwann cells-can have therapeutic effects in neurological diseases.Glial cells are increasingly recognized as important targets for the treatment of these disorders.Furthermore,the article emphasizes the emerging field of bioluminescent optogenetics,which combines optogenetic principles with bioluminescent proteins to visualize and manipulate neural activity in real time.By integrating molecular genetics techniques with bioluminescence,researchers have developed methods to monitor neuronal activity efficiently and less invasively,enhancing our understanding of central nervous system function and the mechanisms of plasticity in neurological disorders beyond traditional neurobiological methods.Evidence has shown that optogenetic modulation can enhance motor axon regeneration,achieve complete sensory reinnervation,and accelerate the recovery of neuromuscular function.This approach also induces complex patterns of coordinated motor neuron activity and promotes neural reorganization.Optogenetic approaches hold immense potential for therapeutic interventions in the central nervous system.They enable precise control of neural circuits and may offer new treatments for neurological disorders,particularly spinal cord injuries,peripheral nerve injuries,and other neurodegenerative diseases.
基金supported by Van Yüzüncü Yıl University,Scientific Research Projects Coordination Unit(Project No:SDK-2025-11935)Van Yüzüncü Yıl University,Scientific Research Projects Coordination Unit for supporting the study。
文摘Mount Kandil is situated in the eastern sector of the EAHP(Eastern Anatolian High Plateau),to the south of the Lesser Caucasus.The mountain lies at the westernmost end of the Aras Mountains,which extends approximately 80 km along a NW-SE axis.With a summit reaching~3214 m(a.s.l.),Mount Kandil is a stratovolcano that,like many other peaks within the EAHP and the Lesser Caucasus,experienced significant environmental changes during Late Pleistocene.Among these,glacial processes stand out as the most profound,having distinctly shaped the mountains geomorphic landscape.This study presents,for the first time,a comprehensive analysis of the glacial morphology of Mount Kandil based on multiple datasets.Field-based morphological observations indicate that an area of approximately 32.62 km^(2)has been sculpted by glacial activity.Within six glaciated regions on Mount Kandil,25 cirques and 6 glacial valleys have been identified.In addition,moraines in various locations exhibit characteristic morphologies.Furthermore,valley glaciers are inferred to have descended to altitudes as low as~2000 m.The paleoequilibrium line(p ELA)was estimated to use AABR method within GIS,yielding a mean pELA of~2730 m.Ice thickness modelling indicates that the thickness of glaciers in the Kandil Mountain valleys reaches up to~350 m.Due to its orographic extension,Mount Kandil is exposed to humid northwest winds and receives substantial frontal precipitation(~686 mm annually).The compiled geomorphic,cartographic and morphometric parameters suggest that the glaciation dynamics of Mount Kandil—situated between the Southeastern Taurus and the Lesser Caucasus—closely resemble those observed in the Lesser Caucasus.This indicates that glaciation was primarily governed by northern atmospheric systems with additional influences from southerly or westerly winds.The integrated data also underscores the role of multiple atmospheric systems in controlling the glaciation regime around the Lesser Caucasus.Additionally,findings on regional pELA question the common belief that pELA increases eastward in EAHP.
基金supported by the National Natural Science Foundation of China(82574173,82003516)Jiangsu Provincial Natural Science Foundation(BK20251958)+2 种基金Jiangsu Provincial Medical Key Discipline(ZDXK202250)Top Talent Awards Project Fund(RDF-TP-0023,RDF-TP-0030)Postgraduate Research Fund(PGRS2112022)at Xi'an Jiaotong-Liverpool University.
文摘Tuberculosis(TB),one of the oldest infectious diseases caused by Mycobacterium tuberculosis,poses a considerable challenge to global public health.There are approximately 10 million new TB cases worldwide annually,and TB claims the lives of nearly 3 million people each year,making it one of the leading causes of death from a single infectious disease[1].China ranks third globally in terms of TB burden,with approximately 733,000 TB cases reported in 2023[2].Based on the ecological model of health determinants developed by Whitehead and Dahlgren,health determinants can be classified into direct causes.
基金Financial support from the Fundamental Research Funds for Gannan Medical University(No.QD202429)National Natural Science Foundation of China(No.22171206)+2 种基金Natural Science Foundation of Zhejiang Province(No.LZ23B020001)Zhejiang Provincial Ten Thousand Talent Program(No.2023R5244)Open Research Fund of School of Chemistry and Chemical Engineering,Henan Normal University(No.2020ZD04)is gratefully acknowledged.
文摘The Smiles rearrangement is an exceptionally versatile method in organic synthesis,providing a broad canvas for designing cascade reactions that construct new Csp^(2)-Y(Y=C,O,N,S,CO,etc.)bonds.Among the various types of Smiles rearrangement,the radical-type variant has emerged as a more powerful,mild,efficient,and modern synthetic technique compared to its traditional ionic counterpart.This approach excels in generating new(hetero)aromatic migration products,enabling significant advancements in recent years.This tutorial review focuses on the recent progress,since 2016,in the development and application of radical Smiles rearrangement in organic chemistry.Special attention is paid to novel transformations achieved through photochemical,electrochemical,and transition metal catalysis methods.
基金supported by the Shenzhen Hong Kong Joint Funding Project,No.SGDX20230116093645007(to LY)the Shenzhen Science and Technology Innovation Committee International Cooperation Project,No.GJHZ20200731095608025(to LY)+7 种基金Shenzhen Development and Reform Commission’s Intelligent Diagnosis,Treatment and Prevention of Adolescent Spinal Health Public Service Platform,No.S2002Q84500835(to LY)Shenzhen Medical Research Fund,No.B2303005(to LY)Team-based Medical Science Research Program,No.2024YZZ02(to LY)Zhejiang Provincial Natural Science Foundation of China,No.LWQ20H170001(to RL)Basic Research Project of Shenzhen Science and Technology from Shenzhen Science and Technology Innovation Commission,No.JCYJ20210324103010029(to BY)Shenzhen Second People’s Hospital Clinical Research Fund of Guangdong Province High-level Hospital Construction Project,Nos.2023yjlcyj029(to BY),2023yjlcyj021(to LL)Guangdong Basic and Applied Basic Research Foundation,No.2022A1515110679(to LL)China Postdoctoral Science Foundation,No.2022M722203(to GL).
文摘Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological properties and tissue specificity,highlighting its potential as a biomedical material for the repair of severe peripheral nerve injury;however,its role in modulating neuroinflammation post-peripheral nerve injury remains unknown.Here,we aimed to characterize the anti-inflammatory properties of porcine decellularized nerve matrix hydrogel and their underlying molecular mechanisms.Using peripheral nerve injury model rats treated with porcine decellularized nerve matrix hydrogel,we evaluated structural and functional recovery,macrophage phenotype alteration,specific cytokine expression,and changes in related signaling molecules in vivo.Similar parameters were evaluated in vitro using monocyte/macrophage cell lines stimulated with lipopolysaccharide and cultured on porcine decellularized nerve matrix hydrogel-coated plates in complete medium.These comprehensive analyses revealed that porcine decellularized nerve matrix hydrogel attenuated the activation of excessive inflammation at the early stage of peripheral nerve injury and increased the proportion of the M2 subtype in monocytes/macrophages.Additionally,porcine decellularized nerve matrix hydrogel negatively regulated the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB axis both in vivo and in vitro.Our findings suggest that the efficacious anti-inflammatory properties of porcine decellularized nerve matrix hydrogel induce M2 macrophage polarization via suppression of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway,providing new insights into the therapeutic mechanism of porcine decellularized nerve matrix hydrogel in peripheral nerve injury.
基金the China Scholarship Council(CSC)the Uplifting Reciprocal Research Scholarship Program for sponsoring Shixuan Lyu+1 种基金supported by MITACS Accelerate(No.IT39116)the Okanagan Basin Water Board water conservation and quality improvement grant program。
文摘Forests are experiencing more frequent and intense wildfires in Canada,which pose considerable threats to water quantity and quality,particularly during the summer low-flow period when water demand is high.While the impacts of wildfire on hydrology have been widely assessed at the watershed scale,the underlying mechanisms of the responses of summer low flows remain poorly understood.In this study,we employed an integrated research framework that combines hydrometric monitoring with geochemical tracing to evaluate how the 2021 White Rock Lake Wildfire affected summer low flows,and to identify the underlying mechanisms governing these responses in the Okanagan Valley,British Columbia(BC),Canada.We found that(1)summer low flows,represented by Q90(flows exceeded at 90%of the time in summer)significantly increased following the wildfire(p<0.05);(2)summer low flows were primarily regulated by snow water in early summer(July),while dominated by groundwater in late summer(August and September);and(3)enhanced snow water contribution and reduced evapotranspiration(ET)were two primary contributors to the increased summer low flows.Our results provide insights for developing sustainable water management strategies for the region in the context of climate change and increasing forest disturbance.This study also demonstrates that the combination of hydrometric monitoring and geochemical tracing is an effective approach towards uncovering mechanisms that drive low-flow responses.
文摘The poor electrical conductivity of metal-organic frameworks(MOFs)limits their electrocatalytic performance in the oxygen evolution reaction(OER).In this study,a Py@Co-MOF composite material based on pyrene(Py)molecules and{[Co2(BINDI)(DMA)_(2)]·DMA}_(n)(Co-MOF,H4BINDI=N,N'-bis(5-isophthalic acid)naphthalenediimide,DMA=N,N-dimethylacetamide)was synthesized via a one-pot method,leveragingπ-πinteractions between pyrene and Co-MOF to modulate electrical conductivity.Results demonstrate that the Py@Co-MOF catalyst exhibited significantly enhanced OER performance compared to pure Co-MOF or pyrene-based electrodes,achieving an overpotential of 246 mV at a current density of 10 mA·cm^(-2) along with excellent stability.Density functional theory(DFT)calculations reveal that the formation of O*in the second step is the rate-determining step(RDS)during the OER process on Co-MOF,with an energy barrier of 0.85 eV due to the weak adsorption affinity of the OH*intermediate for Co sites.CCDC:2419276.
文摘BACKGROUND Peripheral endovascular intervention(PEVI)is performed using radiation.Radiation has deleterious health consequences for patients and operators.AIM To investigate the gender radiation disparities and procedural outcomes in PEVI.METHODS A prospective observational study was performed in 186 consecutive patients(65±12 years)at an academic medical center from January 2019 to April 2020(mean follow-up of 3.9±3.6 months)comparing the gender radiation disparity and outcomes of PEVI(n=147 underwent intervention,79.0%).Groups were divided into women(n=99,53.2%)and men(n=87,48.4%).Primary endpoints included air kerma,dose area product(DAP),fluoroscopy time,and contrast use.Secondary endpoints included all-cause mortality,acute myocardial infarction,acute kidney injury,stroke,repeat revascularization,major adverse limb event,and the composite of complications.RESULTS Men showed increased DAP compared with women(15221.2±25858.5µGy×m^(2) vs 9251.7±9555.3µGy×m^(2),P=0.047),but no significant difference in air kerma or any other primary endpoints.In the secondary endpoints,no significant diffe-rence was found between gender.CONCLUSION Men had increased DAP indicating more radiation absorption in the exposed area.Gender outcomes showed no difference in complications.Thus,PEVI can be safely performed in men or women.
基金supported by the Discovery Grants program of the Natural Sciences and Engineering Research Council of Canada(No.RGPIN-2021-03553)the Canadian Research Chair in dendroecology and dendroclimatology(CRC-2021-00368)+3 种基金the Ministère des Ressources Naturelles et des Forèts(MRNF,Contract no.142332177-D)the Natural Sciences and Engineering Research Council of Canada(Alliance Grant No.ALLRP 557148-20,obtained in partnership with the MRNF and Resolute Forest Products)the Fonds de recherche du Qu ebec–Nature et technologies(Partnership Research Program on the Contribution of the Forestry Sector to Climate Change MitigationGrant No.2022-0FC-309064)。
文摘Xylogenesis,the process through which wood cells are formed,results in the long-term storage of carbon in woody biomass,making it a key component of the global carbon cycle.Understanding how environmental drivers influence xylogenesis during the growing season is therefore of great interest.However,studying shortterm drivers of wood production using xylogenetic data is complicated by the usual sampling scheme and the influence of eccentric growth,i.e.,heterogeneous growth around the stem.In this study,we improve xylogenesis research by introducing a statistical approach that explicitly considers seasonal phenology,short-term growth rates,and growth eccentricity.To this end,we developed Bayesian models of xylogenesis and compared them with a conventional method based on the use of Gompertz functions.Our results show that eccentricity generated high temporal autocorrelation between successive samples,and that explicitly taking it into account improved both the representativeness of phenology and intra-ring variability.We observed consistent short-term patterns in the model residuals,suggesting the influence of an unaccounted-for environmental variable on cell production.The proposed models offer several advantages over traditional methods,including robust confidence intervals around predictions,consistency with phenology,and reduced sensitivity to extreme observations at the end of the growing season,often linked to eccentric growth.These models also provide a benchmark for mechanistic testing of short-term drivers of wood formation.
基金supported by the National Natural Science Foundation of China(No.51878292).
文摘Large-scale CO_(2)emissions have exacerbated the greenhouse effect,reinforcing the critical need for efficient CO_(2)mitigation methods.Plasma-catalytic technology enables CO_(2)conversion under mild conditions,especially for CO_(2)methanation(the Sabatier reaction),which has attracted significant attention due to its economic benefits and the potential for safe energy transportation via existing natural gas pipelines.The development of high-performance CO_(2)methanation catalysts remains an ongoing and long-term objective,and there is a lack of adequate in-situ characterization techniques to investigate the mechanisms.This study focuses on the Ni/La_(2)O_(3)(LN)catalyst and introduces two CO_(2)activation strategies through F and Na modifications:the Ni-Ov-Ni site activation with electron transfer from Ni0 under low-power conditions and basic site activation under high-power conditions.The LN-NaF catalysts enhance CO_(2)methanation activity across the entire power range compared to LN,achieving a CO_(2)conversion of 86.3%and CH4 selectivity of 99.4%.Additionally,LN-F(h)reaches a CH4 yield 4.15 times higher than that of LN at low power.Furthermore,in-situ diffuse reflectance infrared Fourier transform(DRIFT)spectroscopy with a self-made reactor are performed under plasma-catalytic conditions to reveal the CO_(2)adsorption and conversion mechanisms,indicating that different dopants(F,Na,and NaF)exhibit promoting effects on different intermediates,resulting in variations in CO_(2)methanation activity.This study provides valuable insights for improving catalyst performance and a thorough comprehension of mechanisms in CO_(2)methanation.
基金Supported by the Central High Level Hospital Clinical Research Funding(No.BJ-2024-089).
文摘AIM:To explore the causal relationship between several possible behavioral factors and high myopia(HM)using multivariable Mendelian randomization(MVMR)approach and to find the mediators among them with mediation analysis.METHODS:The causal effects of several behavioral factors,including screen time,education time,time spent outdoors,and physical activity,on the risk of HM using univariable Mendelian randomization(MR)and MVMR analyses were first assessed.Genome-wide association study summary statistics of serum metabolites were also used in mediation analysis to determine the extent to which serum metabolites mediate the effects of behavioral factors on HM.RESULTS:MR analyses indicated that both increased time spent outdoors and a higher frequency of moderate physical activity significantly reduced the risk of HM.Further MVMR analysis confirmed that moderate physical activity independently contributed to a lower risk of HM.Additionally,MR analyses identified 13 serum metabolites significantly associated with HM,of which 12 were lipids and one was an amino acid derivative.Mediation analysis revealed that six lipid metabolites mediated the protective effects of moderate physical activity on HM,with the highest mediation proportion observed for 1-(1-enyl-palmitoyl)-GPC(p-16:0;30.83%).CONCLUSION:This study suggests that in addition to outdoor time,moderate physical activity habits may have an independent protective effect against HM and pointed to lipid metabolites as priority targets for the prevention due to low physical activity.These results emphasize the importance of physical activity and metabolic health in HM and underscore the need for further study of these complex associations.
基金supported by European Union-NextGeneration EU under the Italian University and Research(MUR)National Innovation Ecosystem grant ECS00000041-VITALITY-CUP E13C22001060006(to MdA)。
文摘Stroke is a major cause of death and disability worldwide.It is characterized by a highly interconnected and multiphasic neuropathological cascade of events,in which an intense and protracted inflammatory response plays a crucial role in worsening brain injury.Neuroinflammation,a key player in the pathophysiology of stroke,has a dual role.In the acute phase of stroke,neuroinflammation exacerbates brain injury,contributing to neuronal damage and blood–brain barrier disruption.This aspect of neuroinflammation is associated with poor neurological outcomes.Conversely,in the recovery phase following stroke,neuroinflammation facilitates brain repair processes,including neurogenesis,angiogenesis,and synaptic plasticity.The transition of neuroinflammation from a harmful to a reparative role is not well understood.Therefore,this review seeks to explore the mechanisms underlying this transition,with the goal of informing the development of therapeutic interventions that are both time-and context-specific.This review aims to elucidate the complex and dual role of neuroinflammation in stroke,highlighting the main actors,biomarkers of the disease,and potential therapeutic approaches.
文摘Artificial intelligence(AI)-augmented contrast-enhanced ultrasonography(CEUS)is emerging as a powerful tool in liver imaging,particularly in enhancing the accuracy of Liver Imaging Reporting and Data System(known as LI-RADS)classi-fication.This review synthesized published data on the integration of machine learning and deep learning techniques into CEUS,revealing that AI algorithms can improve the detection and quantification of contrast enhancement patterns.Such improvements led to more consistent LI-RADS categorization,reduced interoperator variability,and enabled real-time analysis that streamlined work-flow.The enhanced sensitivity of AI tools facilitated better differentiation between benign and malignant lesions,ultimately optimizing patient management.These advances suggest that AI-augmented CEUS could transform liver imaging by providing rapid,reliable,and objective assessments.However,the review also highlighted the need for further large-scale,multicenter studies to fully validate these findings and ensure the safe integration of AI into routine clinical practice.INTRODUCTION International hepatology society guidelines have established contrast-enhanced computed tomography(CT)and contrast-enhanced magnetic resonance imaging(MRI)as the imaging modalities of choice for diagnosing hepatocellular carcinoma(HCC)lesions larger than 1 cm.MRI remains the gold standard for detecting small HCC nodules in cirrhotic livers due to its superior soft-tissue contrast and functional imaging capabilities.However,early or atypical presentations remain challenging for differential diagnosis,staging,and treatment planning.In these scenarios contrast-enhanced ultrasonography(CEUS)is a valuable second-line tool,offering real-time,radiation-free evaluation and repeatability for follow-up.A recent meta-analysis of head-to-head studies reported comparable diagnostic performance between CEUS and CT/MRI with pooled sensitivities and specificities of 0.67/0.88 for CEUS vs 0.60/0.98 for CT/MRI in non-HCC malignancies,and similar specificities for HCC diagnosis(0.70 for CEUS vs 0.59 for CT;0.81 for CEUS vs 0.79 for MRI)[1].Given the limitations of individual imaging modalities,hybrid techniques and multimodal approaches are gaining traction for improving lesion detection,especially in cases where standard methods fall short.Artificial intelligence(AI)has emerged as a powerful tool in medical imaging,enhancing diagnostic accuracy and reliability across platforms.In CEUS liver imaging dynamic enhancement patterns often challenge consistent interpretation across observers.AI holds particular promise for standardizing assessments.The growing complexity of liver tumor evaluation has also driven interest in approaches that integrate serum bio-markers with advanced imaging.However,no single strategy currently meets all the diagnostic and prognostic re-quirements.Recent studies highlighted the potential of AI to bridge this gap by enabling precise image interpretation and facilitating the integration of heterogeneous clinical and imaging data[2].Altogether the convergence of CEUS with AI and radiomics offers a dynamic,quantitative,and potentially reproducible paradigm for liver lesion assessment,comple-menting traditional imaging methods.This review aimed to provide an overview of current advances in AI-driven CEUS for liver lesion assessment with a particular focus on automated Liver Imaging Reporting and Data System(LI-RADS)classification,radiomics-based models,and future clinical integration.While another recent systematic review[3]provided a comprehensive analysis of AI applications in CEUS,our approach offers a targeted perspective,emphasizing LI-RADS-centered scoring,automated lesion characterization,and clinical utility,particularly in the context of HCC diagnosis and management.In the methodological process of this narrative mini-review,the literature selection was primarily based on targeted PubMed searches.ChatGPT-4o(OpenAI)[4]was employed to assist in refining query parameters and identifying relevant,up-to-date peer-reviewed sources on CEUS-based AI applications.
文摘Cirrhosis represents the end stage of chronic liver disease,significantly reducing life expectancy as it progresses from a compensated to a decompensated state,leading to serious complications.Recent improvements in medical treatment have created a shift in cirrhosis management.Various causes,including hepatitis viruses,alcohol consumption,and fatty liver disease,contribute to cirrhosis and are closely linked to liver cancer.The disease develops through hepatocyte necrosis and regeneration,resulting in fibrosis and sinusoidal capillarization,leading to portal hypertension and complications such as ascites,hepatic encephalopathy,and organ dysfunction.Cirrhosis also holds an increased risk of hepatocellular carcinoma.Diagnosing cirrhosis involves assessing fibrosis scores through blood tests and measuring liver stiffness through elastography.Liver transplantation is the definitive treatment for endstage liver disease and acute liver failure.
基金The authors extend their appreciation to King Saud University,Saudi Arabia for funding this work through the Ongoing Research Funding Program(ORF-2025-704),King Saud University,Riyadh,Saudi Arabia.
文摘A novel siphon-based divide-and-conquer(SbDaC)policy is presented in this paper for the synthesis of Petri net(PN)based liveness-enforcing supervisors(LES)for flexible manufacturing systems(FMS)prone to deadlocks or livelocks.The proposed method takes an uncontrolled and bounded PN model(UPNM)of the FMS.Firstly,the reduced PNM(RPNM)is obtained from the UPNM by using PN reduction rules to reduce the computation burden.Then,the set of strict minimal siphons(SMSs)of the RPNM is computed.Next,the complementary set of SMSs is computed from the set of SMSs.By the union of these two sets,the superset of SMSs is computed.Finally,the set of subnets of the RPNM is obtained by applying the PN reduction rules to the superset of SMSs.All these subnets suffer from deadlocks.These subnets are then ordered from the smallest one to the largest one based on a criterion.To enforce liveness on these subnets,a set of control places(CPs)is computed starting from the smallest subnet to the largest one.Once all subnets are live,this process provides the LES,consisting of a set of CPs to be used for the UPNM.The live controlled PN model(CPNM)is constructed by merging the LES with the UPNM.The SbDaC policy is applicable to all classes of PNs related to FMS prone to deadlocks or livelocks.Several FMS examples are considered from the literature to highlight the applicability of the SbDaC policy.In particular,three examples are utilized to emphasize the importance,applicability and effectiveness of the SbDaC policy to realistic FMS with very large state spaces.
基金would like to thank the Deanship of Graduate Studies and Scientific Research at Qassim University for financial support(QU-APC-2025).
文摘Automated and accurate movie genre classification is crucial for content organization,recommendation systems,and audience targeting in the film industry.Although most existing approaches focus on audiovisual features such as trailers and posters,the text-based classification remains underexplored despite its accessibility and semantic richness.This paper introduces the Genre Attention Model(GAM),a deep learning architecture that integrates transformer models with a hierarchical attention mechanism to extract and leverage contextual information from movie plots formulti-label genre classification.In order to assess its effectiveness,we assessmultiple transformer-based models,including Bidirectional Encoder Representations fromTransformers(BERT),ALite BERT(ALBERT),Distilled BERT(DistilBERT),Robustly Optimized BERT Pretraining Approach(RoBERTa),Efficiently Learning an Encoder that Classifies Token Replacements Accurately(ELECTRA),eXtreme Learning Network(XLNet)and Decodingenhanced BERT with Disentangled Attention(DeBERTa).Experimental results demonstrate the superior performance of DeBERTa-based GAM,which employs a two-tier hierarchical attention mechanism:word-level attention highlights key terms,while sentence-level attention captures critical narrative segments,ensuring a refined and interpretable representation of movie plots.Evaluated on three benchmark datasets Trailers12K,Large Movie Trailer Dataset-9(LMTD-9),and MovieLens37K.GAM achieves micro-average precision scores of 83.63%,83.32%,and 83.34%,respectively,surpassing state-of-the-artmodels.Additionally,GAMis computationally efficient,requiring just 6.10Giga Floating Point Operations Per Second(GFLOPS),making it a scalable and cost-effective solution.These results highlight the growing potential of text-based deep learning models in genre classification and GAM’s effectiveness in improving predictive accuracy while maintaining computational efficiency.With its robust performance,GAM offers a versatile and scalable framework for content recommendation,film indexing,and media analytics,providing an interpretable alternative to traditional audiovisual-based classification techniques.
基金supported by the Ministry of Science and Technology of China(2020YFA0908900)National Natural Science Foundation of China(21935011 and 82072490)+1 种基金Shenzhen Science and Technology Innovation Commission(KQTD20200820113012029 and KJZD20230923114612025)Guangdong Provincial Key Laboratory of Advanced Biomaterials(2022B1212010003).
文摘Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.
